Practical Approaches to Measuring and Interpreting Alzheimer’s Disease Biomarkers

S., according to the Alzheimer’s Association. Two such treatments, the monoclonal antibodies lecanemab and donanemab, were approved by the Food and Drug Administration in 2023 and 2024, respectively. They work by identifying and removing amyloid plaques from the brain, which slows and delays cognitive decline.

These breakthrough treatments have also brought more attention to testing for AD, which can help clinicians to determine which patients with mild-stage disease are good candidates for the medications. “These two new drugs have brought out interest in the Alzheimer’s disease biomarker field in clinical practice,” said Danting Liu, PhD, a clinical chemistry fellow in the clinical immunoassay laboratory in the department of laboratory medicine and pathology at the Mayo Clinic in Rochester, Minnesota. At a roundtable session at ADLM 2025 (formerly the AACC Annual Scientific Meeting & Clinical Lab Expo), Liu will discuss the resulting opportunities and challenges for the clinical lab and clarify confusion among clinicians about which tests to use.

Typically, AD biomarkers can be measured in two ways: through cerebrospinal fluid (CSF) for Aß42/40 ratio and p-tau181/Aß42 ratio; and through blood for p-tau217 and Aß42/40. The blood-based tests, which measure biomarkers in plasma, are less invasive and easier to collect, Liu said. This often makes them more attractive to clinicians who want to pick the least painful test for their patients.

But blood-based tests are not as accurate as CSF-based ones because plasma contains lower concentrations of the biomarkers than CSF. That doesn’t mean blood-based tests are worthless, but rather that clinicians must take multiple factors into consideration when choosing an assay. “This session is timely in that it helps clinics and lab professionals know the strengths and limitations of these tests,” Liu said.

She will guide attendees through case studies and interactive discussions, where they will learn about assay selection, handling biomarker variability, and enhancing patient care through the careful applications of AD biomarkers.

Just as selecting an assay is not cut and dried, neither is interpreting results. For example, the CSF test isn’t an individual assay but instead a panel, where results are used to calculate ratios. “Sometimes a ratio might be positive, but other markers may be in the normal range,” Liu said.

The session will use real patient data to show how the tests work and pinpoint where confusion over results often comes in. “We’re going to bring some cases to show different patterns and how to interpret those in different conditions,” Liu added. She’ll give attendees actionable advice on how to “interpret the results when they are discordant or they are in rare patterns.”

Liu anticipates that discussions around the use of these tests and their interpretation will become more critical as demand for amyloid-targeting therapies grows and AD becomes more prevalent due to an aging population. According to the Alzheimer’s Association, AD already costs an estimated $384 billion in health and long-term care expenses. The monoclonal antibody treatments are pricey as well. For example, Leqembi, the brand name for lecanemab, costs $26,500 per year, and CMS expects to spend $3.5 billion on it in 2025, according to a report from Stat News.

“I have encountered many questions from clinicians about when to offer these tests and how to choose between them,” Liu said. “In real practice, the interpretation of those biomarkers isn’t always straightforward, so I thought this would be a great opportunity to share our knowledge and experience,” she added.